Bombesin antagonists inhibit proangiogenic factors in human experimental breast cancers

A. M. Bajo, A. V. Schally, K. Groot, K. Szepeshazi

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

The overexpression of angiogenic factors such as vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF) and insulin-like growth factors (IGFs) plays a role in the migration and proliferation of endothelial cells in many cancers, Consequently, we investigated the effects of bombesin/gastrin-releasing peptide (GRP) antagonists on the expression of these angiogenic factors, the activities of matrix metalloproteinases (MMPs)-2 and -9, as well as the vascular density in MDA-MB-435 human oestrogen-independent breast cancers. Nude mice bearing orthotopic xenografts of MDA-MB-435 breast cancers were treated with bombesin/ GRP antagonists for 6 weeks. Daily administration of 20 μg of RC-3095 or 10 μg of RC-3940-II significantly decreased the weight of MDA-MB-435 cancers by 44 and 53%, respectively. The inhibition of tumour growth was associated with a substantial reduction in the expression of mRNA and protein levels of basic fibroblast growth factor (bFGF), IGF-II and VEGF-A in the tumours. Both bombesin/GRP antagonists significantly decreased the vessel density of the tumours by about 37%, as shown by immunohistochemical detection of vessels on tumour slides. Gelatinolytic activities, detected by zymography, revealed a 33-46% reduction in MMP-9 activity after the treatment with either antagonist. In vitro studies revealed that MDA-MB-435 cells secrete bFGF, IGF-II and VEGF-A, and the secretion of these factors is inhibited by RC-3095 and RC-3940-II. This study demonstrates the antiangiogenic effect of bombesin/GRP antagonists RC-3095 and RC-3940-II, and underscores their possible therapeutic application for treatment of breast cancers.

Original languageEnglish (US)
Pages (from-to)245-252
Number of pages8
JournalBritish Journal of Cancer
Volume90
Issue number1
DOIs
StatePublished - Jan 12 2004
Externally publishedYes

Keywords

  • Angiogenesis factors
  • Breast cancer
  • Cancer therapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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